Novel Gene Therapy Approach to PD Reported Safe and Tolerable: What Does It Mean for Patients?
On Friday, June 22, news outlets reported the publication in the journal Lancet of results from a Phase 1 trial conducted to determine the safety of a novel gene therapy approach to Parkinson's. The trial, conducted in 12 patients, determined that the approach was safe, and researchers also reported that it seemed to improve PD symptoms without causing side effects.
The Michael J. Fox Foundation spoke to Thomas Wichmann, MD, associate professor of neurology at Emory University in Atlanta, Georgia, about how people with Parkinson's should interpret the news.
Q: The researchers in this study targeted GAD. Can you give a little background on what we know about this gene?
As you state correctly, this was a phase-1 safety trial. It had an unblinded, non-randomized, open-label design, as is often the case with safety trials. What this jargon really means is that the study was open to potential biases. The study was not designed (and therefore cannot) really inform us about the effectiveness of the new therapy.
It is, however, encouraging that the authors found that the therapy could be safely applied, and that no serious adverse events occurred during an observation period of more than three years in some of the patients. The apparent beneficial effects are also interesting, and should be reason to consider planning larger blinded and randomized studies to look at the true benefit of the therapy. Overall, I am cautiously optimistic regarding the use of this therapy. The question whether it will provide benefits beyond those of the existing pharmacologic and surgical treatments is completely open at this point.
In general, the new findings are significant, because they show that gene therapy can safely be done in Parkinson's disease. This may open the door not only to GAD-delivery approaches, but also to other gene therapies for Parkinson's disease.
Q: Is there anything we haven't covered that you feel people should keep in mind when it comes to this study?
TW: This study was carefully conducted. Specifically, the addition of imaging data was a very positive step. The imaging data showed that the therapy has effects that in some sense are similar to those of deep brain stimulation of the subthalamic nucleus.
There are a number of issues that I would have liked to see addressed in greater detail. One is the question whether the patients that were enrolled in this study had significant dyskinesias, and whether such involuntary movements changed with the treatment. Secondly, while the paper states that there were no changes in neuropsychiatric tests, the extent of the neuropsychiatric evaluations is not entirely clear from the text. Changes in cognition and mood occur as side effects of DBS therapy, and it will be interesting to find out in the future how the two treatment modalities compare in this regard. Finally, it would have been of interest to know how specific the treatment was. While the injections targeted the subthalamic nucleus, the injected volume was large enough to have potentially also affected neighboring areas. All of these questions will have to be addressed in the future.